Aim 1. While the observation that sleep is conserved suggests that it provides important fitness benefits, the relationship between sleep and evolutionary fitness is not known. We have developed a novel approach to investigate the possible effect of sleep on reproductive fitness by quantifying the phenotypic and genetic co-variation between sleep and traits that are important determinants of reproductive success in Drosophila melanogaster. Different morphological, behavioral, and life-history factors may contribute to reproductive success. The first trait we are focusing on is the ovarioles, tubes in the fly ovary that produce oocytes. Numbers of ovarioles strongly affect reproductive fitness in female flies by limiting maximum fecundity. We are counting the numbers of ovarioles in females of the Drosophila Genetic Reference Panel (DGRP), a collection of inbred lines derived from a wild North American population. Preliminary analysis reveals that ovariole number varies significantly among lines in the DGRP and has a strong heritable component. Since the DGRP is a community resource that is fully sequenced, we will be able to identify polymorphisms associated with ovariole number and examine the degree to which these polymorphisms overlap with those previously identified for sleep. Aim 2. A previous genome-wide association study (GWAS) of sleep in Drosophila revealed 8,127 polymorphisms associated with fourteen sleep traits. Some of these polymorphisms fall within genes, and some are intergenic. For those polymorphisms falling within genes, we have identified those with the greatest homology to human genes. We will further explore the role of these genes in sleep using flies. Promising candidate genes from these fly studies will be tested in a mouse model. Sleep-associated polymorphisms falling into intergenic regions are more challenging, as the sequence between genes is not expected to be conserved across species. We have therefore undertaken a preliminary in silico approach to determine if any of these polymorphisms impact conserved aspects of gene regulation.